Human monkeypox is a viral zoonotic disease that occurs mostly in the rain forests of central and western Africa. However, the disease recently emerged in the United States in imported wild rodents from Africa. Monkeypox has a clinical presentation very similar to that of ordinary forms of smallpox, including flulike symptoms, fever, malaise, back pain, headache, and characteristic rash. Given this clinical spectrum, differential diagnosis to rule out smallpox is very important. There are no licensed therapies for human monkeypox; however, the smallpox vaccine can protect against the disease. The discontinuation of general vaccination in the 1980s has given rise to increasing susceptibility to monkeypox virus infection in the human population. This has led to fears that monkeypox virus could be used as a bioterrorism agent. Effective prevention relies on limiting the contact with infected patients or animals and limiting the respiratory exposure to infected patients.

ACAM2000™: The new smallpox vaccine for United States Strategic National Stockpile Aysegul Nalca, Elizabeth E ZumbrunCenter for Aerobiological Sciences, US Army Medical Research Institute of Infectious Diseases (USAMRIID), Fort Detrick, MD, USA Smallpox was eradicated more than 30 years ago, but heightened concerns over bioterrorism have brought smallpox and smallpox vaccination back to the forefront. The previously licensed smallpox vaccine in the United States, Dryvax® (Wyeth Laboratories, Inc.), was highly effective, but the supply was insufficient to vaccinate the entire current US population. Additionally, Dryvax® had a questionable safety profile since it consisted of a pool of vaccinia virus strains with varying degrees of virulence, and was grown on the skin of calves, an outdated technique that poses an unnecessary risk of contamination. The US government has therefore recently supported development of an improved live vaccinia virus smallpox vaccine. This initiative has resulted in the development of ACAM2000™ (Acambis, Inc.™), a single plaque-purified vaccinia virus derivative of Dryvax®, aseptically propagated in cell culture. Preclinical and clinical trials reported in 2008 demonstrated that ACAM2000™ has comparable immunogenicity to that of Dryvax®, and causes a similar frequency of adverse events. Furthermore, like Dryvax®, ACAM2000™ vaccination has been shown by careful cardiac screening to result in an unexpectedly high rate of myocarditis and pericarditis. ACAM2000™ received US Food and Drug Administration (FDA) approval in August 2007, and replaced Dryvax® for all smallpox vaccinations in February 2008. Currently, over 200 million doses of ACAM2000™ have been produced for the US Strategic National Stockpile. This review of ACAM2000™ addresses the production, characterization, clinical trials, and adverse events associated with this new smallpox vaccine.Keywords: smallpox, vaccinia, variola, vaccine, efficacy, safety

The smallpox vaccine Dryvax, a live vaccinia virus (VACV), protects against smallpox and monkeypox, but is contraindicated in immunocompromised individuals. Because Abs to VACV mediate protection, a live virus vaccine could be substituted by a safe subunit protein-based vaccine able to induce a protective Ab response. We immunized rhesus macaques with plasmid DNA encoding the monkeypox orthologs of the VACV L1R, A27L, A33R, and B5R proteins by the intradermal and i.m. routes, either alone or in combination with the equivalent recombinant proteins produced in Escherichia coli. Animals that received only DNA failed to produce high titer Abs, developed innumerable skin lesions after challenge, and died in a manner similar to placebo controls. By contrast, the animals vaccinated with proteins developed moderate to severe disease (20–155 skin lesions) but survived. Importantly, those immunized with DNA and boosted with proteins had mild disease with 15 or fewer lesions that resolved within days. DNA/protein immunization elicited Th responses and binding Ab titers to all four proteins that correlated negatively with the total lesion number. The sera of the immunized macaques recognized a limited number of linear B cell epitopes that are highly conserved among orthopoxviruses. Their identification may guide future efforts to develop simpler, safer, and more effective vaccines for monkeypox and smallpox.

It is unknown whether smallpox vaccination would protect human immunodeficiency virus type 1 (HIV-1)-infected individuals, because helper CD4+ cells,